Nutritional Considerations in Bipolar Disorder. Simon J. Evans, Ph.D.

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1 Nutritional Considerations in Bipolar Disorder Simon J. Evans, Ph.D.

2 Leave your drugs in the chemist s pot if you can heal the patient with food. Hippocrates, circa 400 B.C.

3 Overview The Brain as a Physical Organ The brain has high metabolic demands and requires delivery of oxygen, energy and nutrients Foods and Mood Disorders There is a relationship between the diet and the incidence of mood disorders Fatty Acids and Bipolar Disorder Omega-3s and -6 may play roles in bipolar risk, severity and response to medications

4 The Brain is Metabolic Machine

5 The Brain Needs Nutrients, Too Your Brain weighs about 2% of you body weight but uses more than its share of energy and nutrients. 15% of cardiac output (blood supply) 20% of oxygen consumption 25% of glucose utilization (energy supply) Your Brain is about 65% Fat! Large amounts of polyunsaturated fat High concentration of the omega-3, DHA

6 The Brain is Influenced by Metabolic Health of the Body

7 Overview The Brain as a Physical Organ The brain has high metabolic demands and requires delivery of oxygen, energy and nutrients Foods and Mood Disorders There is a relationship between the diet and the incidence of mood disorders Fatty Acids and Bipolar Disorder Omega-3s and -6 may play roles in bipolar risk, severity and response to medications

8 Essential Nutrients Implicated in Mood Disorders Vitamins Folic Acid Vitamin D Vitamin B12 Vitamin B6 Thiamin Vitamin E Minerals Calcium Selenium Zinc Magnesium Essential Nutrients Omega-3s Tryptophan Other Amino Acids

9 blood sugar Acute Mood Effects of High Glycemic Meals elevated mood (increased dopamine) eat eat eat high glycemic diet low glycemic diet target blood sugar time irritable mood Hunger Cravings, Energy Crash

10 In middle-aged participants, a processed food dietary pattern is a risk factor for CES-D depression 5 years later, whereas a whole food pattern is protective. Statistical models adjusted for: gender physical activity age diabetes marital status heart disease energy intake cognitive function employment grade antidepressants use education level The British Journal of Psychiatry (2009) 195:

11 Bipolar Patients have Increased Risk for Poor Metabolic Health Bipolar Patients as a group have poorer eating habits than the general population. Eat less regular daily meals Report difficulty in obtaining or cooking food Eat foods of poorer nutritional quality Eat foods with an increased glycemic load Bipolar Patients on anti-psychotic medications are at increased risk for metabolic health problems. Increased weight gain Insulin resistance Endothelial dysfunction

12 It s a Balancing Act Poor Sleep Habits Sedentary Behavior Quality Sleep Habits Poor Diet Healthy Diet Experiences Exercise Genetics Risk Factors Protective Factors

13 Overview The Brain as a Physical Organ The brain has high metabolic demands and requires delivery of oxygen, energy and nutrients Foods and Mood Disorders There is a relationship between the diet and the incidence of mood disorders Fatty Acids and Bipolar Disorder Omega-3s and -6 may play roles in bipolar risk, severity and response to medications

14 How Do Fats Fit Into the Picture? The Brain has a high concentration of fat 65% fatty acids by dry weight 15% Polyunsaturated fatty acid 6% omega-3 (DHA) Low serum omega-3s associate with mood and cognitive disorders Major Depression Bipolar Disorder Schizophrenia Suicidal Behavior Violent Behavior Child and Adult ADHD Alzheimer s Dementia and Cognitive Impairment

15 All Omega Fats Are Not Created Equal Omega-6s Omega-3s plant oils short chain fats long chain fats Agranoff (2008) Gastronomica 8(3):79-85

16 Dietary Omega-3 to Omega-6 Ratios Have Changed Simopoulos (1999) Am J Clin Nutr 70:560S-9S

17 Omega-3 Intake Correlates with Mood Disorders Lifetime Prevalence of Bipolar (%) Major Depression 12 Bipolar Disorder r = p < Germany Hungary Switzerland Italy USA Canada Puerto Rico Israel New Zealand China Korea Norway Long Chain Omega-3 FAs (% of Dietary Energy) Iceland Gomez-Pinilla (2008) Nat Rev Neurosci 9(7): Hibbeln et al (2006) Am J Clin Nutr 83(suppl):1483S-93S

18 Dietary Omega-3 Deficiency Alters Brain Chemistry Diet Effects Changes in Behavior and Neurochemistry Anxiety-Like Behavior Dopamine Activity Serotonin Activity Endocanabinoid Activity

19 Conceptual Mechanisms of Omega-3 and Omega-6 Actions extracellular signaling (endocannabinoids, eicosanoids) cleavage from membrane intracellular signal transduction Cross Section of Neuronal Membrane receptor kinetics w-3s and w-6s compete for: membrane incorporation synthesis of eicosanoids elongation by enzymes Intracellular signaling This effects: Immune responsivity Cardiovascular tone Mood circuits Insulin sensitivity

20 Genetic Variants Influence Omega-3 and Omega-6 Levels Baylin et al (2007) Am J Clin Nutr 85:554-60

21 Mood Stabilizers Inhibit Omega-6 Activity in Neurons Rapoport et al. (2009) Brain Res Rev 61:

22 Serum ALA:EPA Serum EPA:DHA Omega-3 Profiles Associate with Personality Traits r = p = r = p= ALA r = 0.38 p = r = 0.43 p = EPA DHA Extraversion Factor Agreeableness Factor

23 FADS 2 Activity Serum ALA:DHA Omega-3 Profiles Associate with Personality Traits r = p = ALA FADS r = 0.41 p = FADS2 EPA DHA Openness Factor

24 Serum Concentration Omega-3 and -6 Profiles Differ in Suicide Attempters n6:n3 serum ratios AA non-attempters attempters EPA non-attempters attempters LA:ALA AA:EPA AA:DHA n6:n3

25 Summary The brain is a physical organ, requiring: A healthy neurovascular system. A supply of quality nutrients and energy. Dietary patterns associate with the development of major depression. Fatty acid intakes associate with the rate of depression and bipolar disorder and alters neurochemistry involved in mood regulation. Diet and genetics interact to control fatty acid profiles. Mood stabilizing medications used to treat bipolar disorder inhibit omega-6 activity. Omega-3 profiles associate with personality factors that may influence the burden of bipolar disease and suicide risk.

26 Research Questions (Studies in Progress) Does a diet high in omega-6 or low in omega-3 influence the burden of disease in bipolar disorder? inhibit medications used to treat mood disorders? Do specific genetic variants that control fatty acid profiles either increase risk for mood disorders or influence the efficacy of mood stabilizing medications? Can dietary interventions aimed at increasing specific fatty acids be protective against developing mood disorders or at least reduce the severity of mood disorders and improve patients responses to medications?

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